11 research outputs found
Recommended from our members
Epidemiological drivers of transmissibility and severity of SARS-CoV-2 in England.
Acknowledgements: We thank all colleagues at PHE and front-line health professionals who have not only driven and continue to drive the daily response to the COVID-19 epidemic in England but also provided the necessary data to inform this study. This work would not have been possible without the dedication and expertise of said colleagues and professionals. The use of pillar-2 PCR testing data, vaccination data, and the variant and mutation data was made possible thanks to PHE colleagues, and we extend our thanks to N Gent and A Charlett for facilitation and insights into these data. The use of serological data was made possible by colleagues at PHE Porton Down, Colindale, and the NHS Blood Transfusion Service. We are particularly grateful to G Amirthalingam and N Andrews for helpful discussions around these data. We thank all the REal-time Assessment of Community Transmission (REACT) Study investigators for sharing PCR prevalence data. We sincerely appreciate Dr. Lloyd Chapman for his thorough review of our preprint manuscript, supplementary materials, and code. His comments and corrections greatly contributed to the completeness, accuracy, and reproducibility of our work. We finally thank the entire Imperial College London COVID-19 response team for support and feedback throughout. The views expressed are those of the authors and not necessarily those of the UK Department of Health and Social Care, the NHS, the National Institute for Health Research (NIHR), PHE, UK Medical Research Council (MRC), UK Research and Innovation, or the EU. This work was supported jointly by the Wellcome Trust and the Department for International Development (DFID; 221350). This work was supported by the Medical Research Council (MRC) Centre for Global Infectious Disease Analysis (grant number MR/R015600/1); this award is jointly funded by the MRC and Foreign, Commonwealth and Development Office (FCDO) under the MRC/FCDO Concordat agreement, and is also part of the European and Developing Countries Clinical Trials Partnership programme supported by the EU. This work was also supported by the National Institute for Health and Care Research (NIHR) Health Protection Research Unit (HPRU) in Modelling and Health Economics, which is a partnership between the UK Health Security Agency (UKHSA), Imperial College London, and the London School of Hygiene & Tropical Medicine (grant code NIHR200908). L.K.W. is funded by the Wellcome Trust (grant number 218669/Z/19/Z). The views expressed are those of the authors and not necessarily those of the UK Department of Health and Social Care (DHSC), FCDO, EU, MRC, NIHR, UKHSA, or Wellcome Trust.As the SARS-CoV-2 pandemic progressed, distinct variants emerged and dominated in England. These variants, Wildtype, Alpha, Delta, and Omicron were characterized by variations in transmissibility and severity. We used a robust mathematical model and Bayesian inference framework to analyse epidemiological surveillance data from England. We quantified the impact of non-pharmaceutical interventions (NPIs), therapeutics, and vaccination on virus transmission and severity. Each successive variant had a higher intrinsic transmissibility. Omicron (BA.1) had the highest basic reproduction number at 8.3 (95% credible interval (CrI) 7.7-8.8). Varying levels of NPIs were crucial in controlling virus transmission until population immunity accumulated. Immune escape properties of Omicron decreased effective levels of immunity in the population by a third. Furthermore, in contrast to previous studies, we found Alpha had the highest basic infection fatality ratio (2.9%, 95% CrI 2.7-3.2), followed by Delta (2.2%, 95% CrI 2.0-2.4), Wildtype (1.2%, 95% CrI 1.1-1.2), and Omicron (0.7%, 95% CrI 0.6-0.8). Our findings highlight the importance of continued surveillance. Long-term strategies for monitoring and maintaining effective immunity against SARS-CoV-2 are critical to inform the role of NPIs to effectively manage future variants with potentially higher intrinsic transmissibility and severe outcomes
Lipid biology of the podocyte—new perspectives offer new opportunities
In the past 15 years, major advances have been made in understanding the role of lipids in podocyte biology. First, susceptibility to focal segmental glomerulosclerosis (FSGS) and glomerular disease is associated with an APOL1 sequence variant, is expressed in podocytes and encodes apolipoprotein L1, an important component of HDL. Second, acid sphingomyelinase-like phosphodiesterase 3b encoded by SMPDL3b has a role in the conversion of sphingomyelin to ceramide and its levels are reduced in renal biopsy samples from patients with recurrent FSGS. Furthermore, decreased SMPDL3b expression is associated with increased susceptibility of podocytes to injury after exposure to sera from these patients. Third, in many individuals with membranous nephropathy, autoantibodies against the phospholipase A(2) (PLA(2)) receptor, which is expressed in podocytes, have been identified. Whether these autoantibodies affect the activity of PLA(2), which liberates arachidonic acid from glycerophospholipids and modulates podocyte function, is unknown. Fourth, clinical and experimental evidence support a role for ATP-binding cassette sub-family A member 1-dependent cholesterol efflux, free fatty acids and glycerophospolipids in the pathogenesis of diabetic kidney disease. An improved understanding of lipid biology in podocytes might provide insights to develop therapeutic targets for primary and secondary glomerulopathies